Cordyceps polysaccharide marker CCP modulates immune responses via highly selective TLR4/MyD88/p38 axis

Carbohydr Polym. 2021 Nov 1:271:118443. doi: 10.1016/j.carbpol.2021.118443. Epub 2021 Jul 16.

Abstract

Cordyceps, one of the most expensive natural health supplements, is popularly used to modulate immune function. However, little is known regarding the underlying mechanism of its immunomodulatory activity. We newly reported a Cordyceps quality marker CCP (Mw 433.778 kDa) which was characterized as a 1,4-α glucan by chemical and spectral analysis and is able to induce significant immune responses of macrophages. Herein, we further investigated the molecular mechanism of CCP's immunomodulatory effects. The results indicate that CCP modulates the TLR4/MyD88/p38 signaling pathway of macrophages, where TLR4 plays a crucial role as verified on TLR4-deficient (TLR4-/-) bone marrow-derived macrophages (BMDMs) and TLR4-/- mice. These findings provide a precise understanding of the molecular mechanism of Cordyceps' immunomodulatory benefits.

Keywords: Cordyceps; Immune responses; Macrophage; Polysaccharide; TLR4/MyD88/p38.

MeSH terms

  • Animals
  • Biomarkers
  • Cordyceps / chemistry*
  • Fungal Polysaccharides / pharmacology*
  • Immunity / drug effects
  • Immunologic Factors / pharmacology*
  • Interleukin-6 / metabolism
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Moths
  • Myeloid Differentiation Factor 88 / metabolism
  • RAW 264.7 Cells
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / deficiency
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Biomarkers
  • Fungal Polysaccharides
  • Immunologic Factors
  • Interleukin-6
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • p38 Mitogen-Activated Protein Kinases